PROJECT SUMMARY Targeted oral anticancer medications (TOAMs) have been the focus of oncology drug development in the past two decades. Although these novel agents contribute to survival improvement in several cancers and are convenient to administer, high drug prices have raised concerns on their affordability and possibly low treatment adherence driven by high out-of-pocket expenses. Current knowledge on the utilization and adherence of TOAMs is largely built upon studies of patients with chronic myelogenous leukemia. It remains unclear whether such knowledge is directly transferrable to other cancers, especially those with both oral and intravenous anticancer medications as viable treatment options. The specific aims of the study are: (1) to examine the utilization patterns of TOAMs as indicated vs. off-label use; (2) to estimate the impact of TOAM use on the overall costs of cancer care, costs of non-hormonal systemic therapies, as well as out-of-pocket payment; (3) to investigate the factors associated with the initiation of a TOAM and time to treatment initiation; and (4) to explore patterns of treatment switches and discontinuation and the associated factors among patients who started their systemic therapy with a TOAM. We will address our research questions using various cohorts of cancer patients extracted from three large claims databases: the SEER-Medicare, MarketScan?, and Health Care Cost Institution data. We will conduct a series of studies to better understand the role of TOAMs in modern cancer care delivery by systematically studying the utilization pattern and economic impact of TOAMs as well as factors affecting the initiation and discontinuation of these novel therapies, paying special attention to financial factors for patients and providers. The findings from our study will inform patients, clinicians, and policy makers of the extent to which off-label prescription of TOAM is practiced in the real-world and the long-term economic impact of TOAM use, and provide critical information to guide reform or re-design of insurance policies to avoid creating financial disincentive to prescribe or use TOAM. Ultimately, the goal of our research is to improve the accessibility, affordability, effectiveness, and safety of TOAMs.